Background Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA).
Objectives To report tofacitinib safety, tolerability and clinical response over 84 months (mo), and radiographic data over 12 mo, in long-term extension (LTE) studies.
Methods Data were from two open-label studies (NCT00413699 [ongoing; database unlocked at March 2015 data-cut] and NCT00661661]) of patients (pts) with RA who completed randomised Phase (P)1/2/3 tofacitinib studies. Pts received tofacitinib 5 or 10 mg BID as monotherapy or with background DMARDs; data were pooled. Primary endpoints: AEs and lab safety. Confirmed data are reported for decreased Hgb, neutrophil and lymphocyte counts, and increases >50% from BL in creatinine. Secondary endpoints: DAS28-4(ESR), HAQ-DI and mTSS. Safety data were included up to 96 mo and efficacy up to Mo 84 (n≤30 post-Mo 84).
Results 4867 pts were treated (mean [max] duration: 1107  days). BL data were from P1/P2/P3 index studies for 90.9% of pts. Total tofacitinib exposure was 14926 pt-years (py); 79.2% of pts maintained initial dose. In total, 2132 pts (43.8%) discontinued (AEs: 1051 [21.6%]; insufficient clinical response: 153 [3.1%]). Most common AE classes: infections and infestations (67.6%) and musculoskeletal/connective tissue disorders (37.3%). Most common AEs: nasopharyngitis (18.1%), upper respiratory tract infection (16.2%) and bronchitis (11.7%). SAEs occurred in 26.8% of pts (incidence rate [IR] 9.7/100 py [95% CI 9.2, 10.2]), and serious infection events (SIEs) in 8.4% of pts (IR 2.8/100 py [95% CI 2.5, 3.0]). Malignancies excluding NMSC were reported in 3.0% of pts (IR 1.0/100 py [95% CI 0.8, 1.1]). IRs for SIEs and malignancies through Mo 96 did not increase vs reported data through Mo 84.1 Decreased Hgb (>30% decrease from BL/Hgb <8 g/dL) occurred in <1.0% of pts. Increased aminotransferases (>3×ULN) occurred in 5.4% (ALT) and 3.1% (AST) of pts. Moderate to severe neutropenia (absolute neutrophil count [ANC] 0.5–1.5×103/mm3) was noted in 1.5% of pts; there were no confirmed cases of ANC <0.5×103/mm3. Confirmed absolute lymphocyte counts <0.5×103/mm3 occurred in 1.3% of pts. Increases >50% from BL in creatinine were seen in 2.4% of pts. Mean DAS28-4(ESR) was 6.29 at BL, 3.74 at Mo 1 and 3.20 at Mo 84. Mean HAQ-DI score was 1.42 at BL, 0.81 at Mo 1 and 0.78 at Mo 84. Radiographic data were available for 1099 pts. Mean mTSS was 24.0 at BL (last P1/P2/P3 index value), 25.1 at Mo 6 and 24.3 at Mo 12. Mean change from BL in mTSS was 0.3 at Mo 6 and 0.2 at Mo 12.
Conclusions Consistent safety and sustained efficacy over 84 mo was seen in pts with RA receiving tofacitinib 5 or 10 mg BID in LTE studies. Changes in mTSS were minimal at Mo 12 in LTE studies.
Wollenhaupt J et al. Arthritis Rheumatol 2014; 66: S375.
Acknowledgement Previously presented (Wollenhaupt J et al. Arthritis Rheumatol 2015; 67 (S10): 1645) and reproduced with permission. This study was funded by Pfizer Inc. Editorial support was provided by S. Johnson of Complete Medical Communications and funded by Pfizer Inc.
Disclosure of Interest J. Wollenhaupt Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc, J. Silverfield Grant/research support from: Pfizer Inc, Speakers bureau: Pfizer Inc, E. B. Lee Consultant for: Pfizer Inc, K. K. Terry Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Kwok Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, I. Lazariciu Consultant for: Pfizer Inc, Employee of: Quintiles Inc, C. Nduaka Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. A. Connell Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. DeMasi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc